RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of giving gemcitabine, doxorubicin, and paclitaxel together with carboplatin in treating patients with advanced bladder or kidney cancer and impaired kidney function.

Condition	Treatment or Intervention	Phase
stage III bladder cancer stage IV bladder cancer transitional cell carcinoma of the bladder metastatic transitional cell cancer of the renal pelvis and ureter localized transitional cell cancer of the renal pelvis and ureter regional transitional cell cancer of the renal pelvis and ureter	Drug: carboplatin  Drug: doxorubicin  Drug: filgrastim  Drug: gemcitabine  Drug: paclitaxel  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: colony-stimulating factor therapy  Procedure: cytokine therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the safety and toxicity of dose-dense carboplatin plus paclitaxel on a weekly schedule given in sequence after gemcitabine and doxorubicin in patients with renal impairment and metastatic or locally advanced transitional cell carcinoma of the urothelium.
• Observe the outcome of this sequential systemic chemotherapy in these patients, or following surgical resection as adjuvant therapy in patients in whom poor renal function precludes the use of cisplatin-based chemotherapy.

OUTLINE: This is a dose escalation study of carboplatin.

Patients receive gemcitabine IV over 10 minutes and doxorubicin IV over 15 minutes for 5 doses on weeks 1, 3, 5, 7, and 9. Filgrastim (G-CSF) is given subcutaneously on days 3 through 10 of each 2-week course. On week 11, patients receive paclitaxel and carboplatin IV over 1 hour weekly for 12 weeks.

Each cohort of 3 patients is entered on sequentially increasing doses of carboplatin. If any patient experiences dose limiting toxicity (DLT), then 6 patients are entered at that dose level. If 3 patients experience DLT at any dose level, the maximum tolerated dose has been surpassed and a total of 6 patients are treated at the previous level.

Patients are evaluated at week 16 and at end of study.

PROJECTED ACCRUAL: There will be 18-30 patients accrued into this study over 9-15 months.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed advanced transitional cell urothelial cancer
• Clinical Stage IV: T any, N1-3, M0; T any, N any, M1; or cT4, Nx, M0 (bladder tumors)
• Pathological Stage III or IV bladder cancer: T any, N1-3, M0; T3b, N0, M0; T4, N0, M0; and T4, Nx, M0
• Pathological Stage III or IV urothelial cancer of the renal pelvis or ureter: T any, N1-3, M0; T3, N0, M0; T4, N0, M0; and surgery has been performed within 10 weeks of initiation of therapy
• Impaired renal function (See Renal function tests)

PATIENT CHARACTERISTICS: Age:

• 18 and over

Performance status:

• Karnofsky 60-100% OR
• ECOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Granulocyte count at least 1,500/mm^3
• Platelet count at least 150,000/mm^3

Hepatic:

• Bilirubin less than 1.5 times normal
• Alkaline phosphatase less than 2 times normal
• SGOT less than 2 times normal

Renal:

• Creatinine greater than 1.5 mg/dL but no greater than 2.5 mg/dL OR
• Creatinine clearance 30-59 mL/min

Cardiovascular:

• Normal cardiac function by history, physical examination, and chest radiograph OR
• If prior cardiac disease, left ventricular ejection fraction must be at least 50% by radionuclide ventriculogram or echocardiogram
• No serious cardiac arrhythmias; including first, second, and third degree heart block
• No New York Heart Association class III or IV heart disease

Other:

• No uncontrolled infection
• No other active cancer, except nonmelanomatous skin cancer and in situ carcinoma of the cervix curatively treated
• Not pregnant
• Effective barrier contraception required for all fertile patients during and for 6 months after therapy (encouraged to continue for 2 years or longer)

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• No prior systemic chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy to the bladder
• At least 4 weeks since any other prior radiotherapy

Surgery:

• See Disease Characteristics

New York
      Memorial Sloan-Kettering Cancer Center, New York,  New York,  10021,  United States; Recruiting
      New York Weill Cornell Cancer Center at Cornell University, New York,  New York,  10021,  United States; Recruiting

Study chairs or principal investigators

Dean F. Bajorin, MD,  Study Chair,  Memorial Sloan-Kettering Cancer Center   

Study ID Numbers:  CDR0000066319; MSKCC-97114; NCI-G98-1438; NCT00003342
Record last reviewed:  September 2004
Last Updated:  February 9, 2005
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00003342
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08